‘Neuromodulation’ is opening up new possibilities for medical therapies by seeking to target and change nerve activity

If something gets on your nerves you usually want to get rid of it as quickly as possible. But from a medical perspective, targeting nerves could offer ways to treat some movement and sensory conditions.

Your body contains a complex network of nerves, which are like electrical information highways, that plays an important role in how you sense the environment – and pain – and how and when parts of your body move.

“Neuromodulation”, which seeks to target and change nerve activity, is opening up new possibilities for medical therapies, according to Dr Ross O’Neill.

He’s CEO of MuteButton, which is developing ways to modulate nerves for the condition tinnitus, where a person “hears” phantom noises like ringing or buzzing. And O’Neill believes that devices are the way forward when looking to home in on nerve activity.

“Pharmaceutical interventions are neither spatially nor temporally targeted,” he says. “A drug blanket bombs the whole system – you don’t know how long it’s going to be in there, and how it acts depends on factors how big you are and how much you eat. With a device you can be much more targeted.”

Going deep into the brain

One way to change how nerves act is to implant electrodes into the brain. Deep-brain stimulation, or DBS, is a surgical therapy for a range of different disorders of the nervous system, explains Dr Madeleine Lowery, a senior lecturer at University College Dublin’s school of electrical, electronic and communications engineering.

“It involves surgically implanting electrodes into a region of the brain known as the basal ganglia – which is a part of the brain involved in movement – and it delivers a very high-frequency stimulus to neurons in that part of the brain,” she says.

“The electrodes are connected by means of a wire that runs just below the skin surface down into the chest cavity to a pulse generator, which looks similar to a standard cardiac pacemaker.”

DBS has been used to treat symptoms in people with movement disorders, such as Parkinson’s disease. You don’t have to look too hard online to find clips of patients whose tremors ease the moment the stimulation is turned on.

Yet the mechanism through which DBS works has yet to be fully understood. Funded through Science Foundation Ireland, Lowery and colleagues are now using computational models to look at how the electrical stimulation could be changing firing patterns in the brain, and how the approach could suppress oscillations that are causing problems. They also want to inform potentially “smarter” ways to go about it.

“At the moment, when the electrode is implanted and the stimulus is turned on it works in an open loop configuration – that means you turn it on and let it go, it doesn’t know anything about what is going on in the body,” says Lowery.

“You could have a system that feeds back information and adjust parameters accordingly.”

Bio-friendly probes

Another way to improve nerve targeting is to design more biocompatible probes, explains Dr Paul Galvin, who heads the life science interface group at Tyndall National Institute in Cork.

“We are actively engaged in designing electrodes that will interface with the neural cells and tissues,” he says, describing how they returning to the drawing board for the electrodes or probes used in DBS.

“Our brains are a bit like jelly in terms of viscosity, and a typical deep-brain probe is more like a needle,” explains Dr Galvin.

“And if you have that rigid probe inside a jelly-like material it is going to cause damage as the brain moves around, but the needle doesn’t. So we want to make electrodes that match the properties of the brain, so they will be truly biocompatible and not build up scar tissue, which could then affect the performance of the probe.”

The group at Tyndall is also working on probes to target specific nerves that lie outside the brain in the body’s periphery.

“One of the biggest opportunities for us is the treatment of chronic pain through the ability to interface with and stimulate peripheral nerves, and we are working with clinicians on that,” says Galvin.

From the outside in

MuteButton also has peripheral nerves in its sights as a less invasive route back into the brain.

The company’s technology, which grew out of research at NUI Maynooth, targets a person’s sense of hearing and touch to “teach” the brain to distinguish real from phantom noise in tinnitus.

The patient listens to a piece of music, and the sound information is simultaneously relayed to sensors placed on the tongue.

Sensory integration centres in the brain can then compare the inputs and distinguish real sounds (the music) from the phantom noises of tinnitus.

O’Neill describes the results of MuteButton’s clinical studies as “encouraging”– and for the future he sees even wider potential for approach of targeting peripheral “afferent” nerves non-invasively in order to affect activity in the brain.

“Our aim is that everywhere that DBS is currently being applied for a condition, we want to investigate non-invasive alternatives by using single or multiple afferent nerve stimulations.”

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